Candidate: The principle investigator, Dr. Karen Westerman, has been an Instructor in the Anesthesia Department at Brigham and Women's Hospital for 2 years. Prior to this I was a Senior Scientist for 5-6 years at a "start-up" gene therapy company designing lentiviral vector systems. Here I request 5 years of mentored research time to make the transition from industry to the academic environment. This mentored time will allow me to become a R01 funded independent investigator and to broaden my knowledge of gene therapy to include that of muscle biology, cell trafficking, and vascular adhesion. To complete the specific aims proposed I have chosen Dr. Paul Allen, an expert in muscle biology, as my sponsor, and an advisory committee composed of Dr. Sean Colgan who's expertise is in cell trafficking, and Dr. Francis Luscinskas who's expertise is in vascular adhesion and cell-to-cell junctions. [unreadable] [unreadable] Environment: This research will be carried out in an environment of a world-class scientific community with the best of both clinical research and basic science (Brigham and Women's Hospital/Harvard Medical School). [unreadable] [unreadable] Research: Here I propose to improve cell-based therapies used for the treatment of muscle diseases such as Muscular Dystrophy by transiently expressing an adhesion molecule, L-selectin, on the surface of transplanted cells to enhance homing and migration of these cells to sites of injury. The specific aims include: 1. To use lentiviral vectors to expression of L-selectin in three cell populations. 2. To test the adhesion and transendothelial migration of L-selectin engineered cells by in vitro assays. 3. To test the homing and migration of L-selectin engineered cells by intra-arterial cell transplantation into a -sarcoglycan deficient mice. The expected results are that transient expression of L-selectin will increase homing and transendothelial migration of these cells to sites of muscle injury. This research could substantially improve cell-based therapy for treatment of muscle disease and open the door to more developed and available cell types to be used for transplantation. [unreadable] [unreadable] Relevance: A major hurdle in treating muscle disease with cell-based therapies is the lack of homing of therapeutic donor cells to injured muscles. Here I propose to express L-selectin, a cell surface adhesion molecule which is responsible for white blood cell homing to sites of injury, on the surface of therapeutic donor cells to improve the homing and migration of these cells to the diseased muscle. [unreadable] [unreadable] [unreadable]